1.New advances in targeted therapy for breast cancer
Jing ZHAO ; Nan WU ; Shichao ZHANG ; Ziwei ZHAO ; Lijuan LI ; Juntian LIU
Chinese Journal of Oncology 2020;42(5):353-361
Objective:Breast cancer is a kind of malignant tumor which seriously endangers women′s health. With the development of molecular biology technology and the further understanding of pathogenesis, the treatment of breast cancer has entered a new era of molecular targeted therapy, and has been making new progress. At present, molecular targeted drugs for the treatment of breast cancer keep emerging, mainly including endocrine therapy targeting estrogen and progesterone receptor (ER/PR), targeted drugs treatment for epidermal growth factor receptor-2 (HER-2); phosphatidylinositol 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway inhibitors, anti-angiogenic drugs, poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA1/2 mutations, cyclin-dependent kinases (CDK) 4/6 inhibitors, etc. Because some signal pathway abnormalities may occur in different molecular types of breast cancer, the same targeted drugs are cross-used in different types.
2.New advances in targeted therapy for breast cancer
Jing ZHAO ; Nan WU ; Shichao ZHANG ; Ziwei ZHAO ; Lijuan LI ; Juntian LIU
Chinese Journal of Oncology 2020;42(5):353-361
Objective:Breast cancer is a kind of malignant tumor which seriously endangers women′s health. With the development of molecular biology technology and the further understanding of pathogenesis, the treatment of breast cancer has entered a new era of molecular targeted therapy, and has been making new progress. At present, molecular targeted drugs for the treatment of breast cancer keep emerging, mainly including endocrine therapy targeting estrogen and progesterone receptor (ER/PR), targeted drugs treatment for epidermal growth factor receptor-2 (HER-2); phosphatidylinositol 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway inhibitors, anti-angiogenic drugs, poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA1/2 mutations, cyclin-dependent kinases (CDK) 4/6 inhibitors, etc. Because some signal pathway abnormalities may occur in different molecular types of breast cancer, the same targeted drugs are cross-used in different types.
3.Clinicopathological analysis of 37 cases of accessory breast cancer
Hailian ZHANG ; Huijiang LI ; Jing ZHAO ; Shichao ZHANG ; Yang ZHAO ; Juntian LIU
Chinese Journal of General Surgery 2019;34(1):27-30
Objective To explore the clinicopathological characteristics,diagnosis,treatment and prognosis of accessory breast cancer.Methods Clinical and pathological data of 37 accessory breast cancer patients from Dec 2005 to Aug 2017 were reviewed.Results 12 patients underwent breast-conserving local wide excision plus axillary lymph node dissection.5 cases were treated by segmental resection and 19 patients by Auchincloss or Halsted mastectomy;One patient abandoned surgery.The most common histological type of accessory breast cancer was infiltrating ductal carcinoma (26 cases,70.3%) followed by adenocarcinoma (4 cases) and miscellaneous type (7 cases).The most common AJCC pathological stages were stage Ⅱ (n =24,65 %),Ⅰ (n =8),Ⅲ(n =3) and Ⅳ (n =2).The median follow-up time was 6 (1-12) years,the followup rate was 100%.Until Dec 2017,7 patients died from metastasis and the others were alive.Conclusions Accessory breast cancer is rare and with poor prognosis.The diagnosis depends on clinical manifestations,imaging and pathology.Surgery is the mainstay therapy,adjuvant chemo therapy is recommanded.
4.The association between the expression and activity of indoleamine 2,3-dioxygenase and the efficacy of neoadjuvant chemotherapy in patients with breast cancer
Yang ZHAO ; Fangxuan LI ; Fengli GUO ; Kun MU ; Nan WU ; Hailian ZHANG ; Juntian LIU
Chinese Journal of Clinical Oncology 2018;45(6):291-296
Objective:To investigate the association between indoleamine 2,3-dioxygenase(IDO)expression in tumor tissue,its periph-eral blood activity, and the efficacy of neoadjuvant chemotherapyin patients with breast cancer. Methods: Immunohistochemistry (IHC)and high-performance liquid chromatography(HPLC)were used to measure IDO protein expression in tumor tissue,and kynuren-ine(Kyn),tryptophan(Trp),and IDO activity(Kyn/Trp)in peripheral blood before neoadjuvant chemotherapy in 53 patients with breast cancer from Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2016.The correlations between the expression and activity of IDO and the efficacy of chemotherapy were analyzed.Results:In tumor tissue,IDO expression-before neoadjuvant chemotherapy was related to clinical tumor stages(P=0.006),node stages(P=0.020),clinical stages(P=0.045),and estrogen receptor(ER)status(P=0.014).High IDO activity before neoadjuvant chemotherapy in peripheral blood was associated with high IDO expression in tumor tissue(P=0.004),and was also correlated with clinical tumor stages(P=0.019)and node stages(P=0.047). Univariate analysis showed that the clinical efficacy of neoadjuvant chemotherapy was associated with pre-chemotherapeutic clinical tumor stages(P=0.049),ER status(P=0.025),and molecular subtype(P=0.014),while pathologic complete response(pCR)was related to pre-chemotherapeutic clinical tumor stages(P=0.014).Importantly,the clinical efficacy of neoadjuvant chemotherapy and pCR were both related to IDO expression and activity before chemotherapy(all P<0.05).Multivariate analysis showed that pre-chemotherapeu-tic IDO activity in peripheral blood was the only independent factor that affected pCR(P=0.032).Conclusions:Tumor tissue IDO expres-sion and peripheral blood IDO activity before chemotherapy were associated with chemotherapy efficacy,and could provide promising information for the clinical prediction of chemotherapy sensitivity.
5.Clinicopathologic characteristics and prognosis of medullary breast carcinoma
Kun MU ; Zizheng WU ; Haifei NIU ; Nan WU ; Jing ZHAO ; Jun ZHANG ; Juntian LIU
Chinese Journal of General Surgery 2017;32(3):211-214
Objective To investigate the clinicopathologic characteristics and prognosis of medullary breast carcinoma.Methods We conducted a retrospective analysis on clinical and pathologic data of 166 patients with medullary breast cancer.Results All the patients were female with a median age of 52 years old.The proportion of patients with stage Ⅰ,Ⅱ and Ⅲ disease was 16.9%,68.1%,15.0%,respectively.The Luminal,HER-2 overexpressing and triple-negative subtypes constituted 31.3%,8.4%,and 60.3%,respectively.There was significant difference in regional lymph node status of medullary breast cancer patients with different molecular types (x2 =18.248,P =0.003),but not in tumor size,TNM stage,histological grade,and expression of Ki67 (all P > 0.05).Multivariate survival analysis indicated that TNM stage was an independent predictor in the prognosis of medullary breast cancer (HR =5.664,P =0.001).All the patients were followed up from 15 months to 145 months with a median follow-up time of 108 months.The 5-year survival rate was 91.5% and the 10-year survival rate was 87.2%.Conclusions The prognosis of medullary breast cancer is favorable.Personalized treatment according to the TNM stage and histopathologic characteristics achieve a favorable prognosis.
6.Second generation sequencing detection breast cancer susceptibility gene variants for risk prediction and clinical treatment
WU NAN ; YU JINPU ; ZHAO JING ; ZHAO YANG ; MU KUN ; ZHANG JUN ; JIN ZHAO ; LIU JUNTIAN
Chinese Journal of Clinical Oncology 2017;44(20):1024-1028
Objective:To investigate the function of breast cancer susceptibility gene variants in predicting breast cancer risk and guid-ing clinical treatment through DNA sequencing. Methods:This study involved 146 patients, 71 high-risk cases, and 55 healthy people, totaling 272 cases. The subjects were treated in Tianjin Medical University Cancer Institute and Hospital from November 2013 to July 2015. Genomic DNA was sequenced by a second generation sequencing platform. All exon areas of six common breast cancer suscepti-bility genes (BRCA1, BRCA2, PTEN, STK11, TP53, and RAP1) were sequenced through amplicon sequencing method. Meaningful vari-ants including single nucleotide variants (SNVs), insertion-deletions (InDels) and nonsense mutations were selected and statistical methods, such as t test andχ2 test, were used to analyze the statistical differences in incidence rates among three groups. Results:A total of 177 meaningful variants were confirmed, including 50 SNVs, 8 nonsense mutations, and 9 InDels. Among the variants, 31 were recorded in the Exome Aggregation Consortium (ExAC), 40 were noted in ClinVar database, and 21 were not encoded in the present da-tabase, which were defined as new variants in this study. Conversely, 57 variants (85.1%) were found in breast cancer patients and high-risk cases, and the incidence of axillary lymph node metastasis (P=0.010) and pathological stages (P=0.002) in mutation positive patients were both higher than mutation negative patients. Moreover, the percentage of family history of cancer (P=0.005) and triple negative breast cancer (P=0.009) were both higher in patients carrying pathogenic mutations than in nonpathogenic patients. Conclu-sion:Breast cancer susceptibility gene variants may not only be a tool used to predict the risk of getting breast cancer but also a mean-ingful guideline for the clinical treatment and prognosis evaluation.
7.Simultaneous quantification of ginsenoside Rg1 and its metabolites by HPLC-MS/MS: Rg1 excretion in rat bile, urine and feces.
Chiyu HE ; Ru FENG ; Yupeng SUN ; Shifeng CHU ; Ji CHEN ; Chao MA ; Jie FU ; Zhenxiong ZHAO ; Min HUANG ; Jiawen SHOU ; Xiaoyang LI ; Yuzhu WANG ; Jinfeng HU ; Yan WANG ; Juntian ZHANG
Acta Pharmaceutica Sinica B 2016;6(6):593-599
Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile, urine, and feces after oral administration (25 mg/kg). Calibration curves offered satisfactory linearity (>0.995) within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80-120%. The excretion recoveries of Rg1, ginsenoside Rh1 (Rh1), and protopanaxatriol (Ppt) in bile, urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were 40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile. Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.
8.Pylori infection distribution in 11 096 individuals
Menghui LI ; Chi ZHANG ; Xiaofeng LIANG ; Shixia LI ; Juntian LIU
Tianjin Medical Journal 2016;44(1):110-113
Objective To investigate the distribution of Helicobacter pylori (Hp) infections among general population in Tianjin. Methods Individuals (n=11 096) who visited our hospital for medical examination and H. Pylori infection screen were included in the research objects. Rapid urease method was utilized to rapidly detect H. pylori infection among the popultion. Individuals were grouped based on their gender, age and occupations, and then were analyzed. Results H. pylori-positive rate was 30.52%(3 386/11 096) in 11 096 individuals, in which there were 34.77%(1 784/5 131) male and 26.86%(1 602/5 965) female respectively. Individuals were divided into 5 groups according to their ages:19 to 29 years old group, 30 to 39 years old group, 40 to 49 years old group, 50 to 59 years old group, 60 to 69 years old group and 70 to 92 years old group. The positive rates of H. pylori increased with age:19.50%( 379/1 944 ) in 19-29 years old group, 25.82%(650/2 517 ) in 30-39 years old group, 31.59%( 908/2 874 ) in 40-49 years old group, 37.48%(915/2 441 ) in 50-59 years old group, 41.09%( 353/859 ) in 60-69 years old group and 39.18%(181/462) in 70-92 years old group. The differences in positive rates between different age groups were all of statistically significant (P<0.05). Individuals were also divided into seven groups according to their occupations: medical worker group, worker group, teacher group, engineer group, clerk group, civil worker group and other career group. The positive rates of H. pylori infection were 25.42%(586/2 305), 29.35%(1 062/3 618), 30.61%(360/1 176), 32.49%(116/357), 33.44%(205/613), 34.52%(455/1 318)and 35.23%(602/1 709) respectively. The positive rate was 25.42% (586/2 305) medical workers, which was lower than that of other occupation groups with significant difference (P<0.002). Conclusion Good management of H. pylori diagnosis and treatment in mid-dle age and elderly together with popularizing knowledge of H.pylori prevention can effectively reduce H.pylori incidence.
9.A case-control study on the association between serum lipid level and the risk of breast cancer
Lijuan WEI ; Chi ZHANG ; Huan ZHANG ; Xi WEI ; Shixia LI ; Juntian LIU ; Xiubao REN
Chinese Journal of Preventive Medicine 2016;50(12):1091-1095
Objective To examine the association between serum lipids,including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the risk and progression of breast cancer in postmenopausal and premenopausal women. Methods A review analysis of female patients who underwent breast cancer surgery and blood lipid metabolism testing in Tianjin One Hospital, from January 2013 to October 2013, was performed. A total of 1 081 patients were included in the final analysis. The control group consisted of 2 981 women without breast cancer. We collected all of the cases' demographic,pathology, lymph nodes metastasis information, was used to testify the difference of serum lipid level between patient and control group, also the postmenopausal and pre-menopausal groups. Results The average age of the patients and control subjects were (51.6±0.3) and (51.0±0.2) years, respectively. Serum TC and LDL-C levels in the patient group, (5.16±0.03) and (3.28±0.26) mmol/L, respectively, were significantly higher than in the control group, (5.02±0.01) and (2.51±0.01) mmol/L, respectively (t values 3.89 and 4.81 and P<0.001). HDL-C levels in the patient group, (1.60±0.01) mmol/L, were significantly lower than in the control group, (1.65±0.01) mmol/L (t=3.90, P<0.001). Similar observations were made in postmenopausal patients. Serum TC and LDL-C levels in the postmenopausal patient group, (5.48±0.04) and (3.27±0.03) mmol/L, respectively, were significantly higher than in control subjects, (5.24±0.02) and (2.71±0.02) mmol/L, respectively (t values 4.75 and 15.30, all P values <0.001). HDL-C levels in postmenopausal patients, (1.60±0.02) mmol/L, were significantly lower than in the control group, (1.69±0.01) mmol/L (t=4.85,P<0.001). In the breast cancer patient group, those at pathological stages 0-Ⅱ had lower TG levels than those at Ⅲ-Ⅳ. These values were (1.19±0.05) and (1.43± 0.09) mmol/L, respectively (t=2.69,P<0.001). Meanwhile, patients with no lymph node metastases had lower TG levels than the lymph node-positive group, with values of (1.15 ± 0.05) and (1.37 ± 0.07) mmol/L, respectively (t=2.53,P=0.012). Conclusion We found that dyslipidemia may affect the incidence of breast cancer, particularly among postmenopausal women. Serum lipids may promote cancer progression through higher TG and low HDL-C levels.
10.A case-control study on the association between serum lipid level and the risk of breast cancer
Lijuan WEI ; Chi ZHANG ; Huan ZHANG ; Xi WEI ; Shixia LI ; Juntian LIU ; Xiubao REN
Chinese Journal of Preventive Medicine 2016;50(12):1091-1095
Objective To examine the association between serum lipids,including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the risk and progression of breast cancer in postmenopausal and premenopausal women. Methods A review analysis of female patients who underwent breast cancer surgery and blood lipid metabolism testing in Tianjin One Hospital, from January 2013 to October 2013, was performed. A total of 1 081 patients were included in the final analysis. The control group consisted of 2 981 women without breast cancer. We collected all of the cases' demographic,pathology, lymph nodes metastasis information, was used to testify the difference of serum lipid level between patient and control group, also the postmenopausal and pre-menopausal groups. Results The average age of the patients and control subjects were (51.6±0.3) and (51.0±0.2) years, respectively. Serum TC and LDL-C levels in the patient group, (5.16±0.03) and (3.28±0.26) mmol/L, respectively, were significantly higher than in the control group, (5.02±0.01) and (2.51±0.01) mmol/L, respectively (t values 3.89 and 4.81 and P<0.001). HDL-C levels in the patient group, (1.60±0.01) mmol/L, were significantly lower than in the control group, (1.65±0.01) mmol/L (t=3.90, P<0.001). Similar observations were made in postmenopausal patients. Serum TC and LDL-C levels in the postmenopausal patient group, (5.48±0.04) and (3.27±0.03) mmol/L, respectively, were significantly higher than in control subjects, (5.24±0.02) and (2.71±0.02) mmol/L, respectively (t values 4.75 and 15.30, all P values <0.001). HDL-C levels in postmenopausal patients, (1.60±0.02) mmol/L, were significantly lower than in the control group, (1.69±0.01) mmol/L (t=4.85,P<0.001). In the breast cancer patient group, those at pathological stages 0-Ⅱ had lower TG levels than those at Ⅲ-Ⅳ. These values were (1.19±0.05) and (1.43± 0.09) mmol/L, respectively (t=2.69,P<0.001). Meanwhile, patients with no lymph node metastases had lower TG levels than the lymph node-positive group, with values of (1.15 ± 0.05) and (1.37 ± 0.07) mmol/L, respectively (t=2.53,P=0.012). Conclusion We found that dyslipidemia may affect the incidence of breast cancer, particularly among postmenopausal women. Serum lipids may promote cancer progression through higher TG and low HDL-C levels.

Result Analysis
Print
Save
E-mail